lncRNA XIST通过Wnt/β-catenin途径抑制胰腺癌的增殖和侵袭

lncRNA XIST Inhibits Pancreatic Cancer Proliferation and Invasion Through Wnt/β-catenin Pathways

目的阐明lncRNA XIST在影响胰腺癌进展中的作用及其潜在机制,以期为胰腺癌的临床治疗提供检测标志物和治疗靶点。方法通过TCGA数据库下载的胰腺癌测序数据,并选择差异基因lncRNA XIST。采用qRT-PCR检测胰腺癌细胞系中lncRNA XIST表达水平;通过转染lncRNA XIST过表达载体构建PANC-1细胞的lncRNA XIST过表达细胞系,并评估过表达lncRNA XIST后PANC-1细胞增殖、迁移和侵袭能力的变化;采用qRT-PCR和Western blotting检测过表达lncRNA XIST的PANC-1细胞中β-catenin、Vimentin和N-cadherin蛋白的表达水平。结果胰腺癌组织中lncRNA XIST水平显著下调(P<0.05);PANC-1、PC-2、SW1990和CFPAC-1细胞系中,PANC-1中lncRNA XIST的表达水平最低;lncRNA XIST过表达可降低PANC-1细胞的增殖、迁移和侵袭能力(P<0.05);lncRNA XIST过表达可下调β-catenin水平(P<0.05),但对Vimentin、N-cadherin水平无明显影响(P>0.05)。结论胰腺癌细胞中lncRNA XIST表达下调,lncRNA XIST过表达可通过激活Wnt/β-catenin途径来抑制胰腺癌细胞的增殖、迁移和侵袭。

Objective To clarify the role and potential mechanism of lncRNA XIST in affecting the progress of pancreatic cancer,and to provide a detection marker and a therapeutic target for clinical treatment of pancreatic cancer.Methods Pancreatic cancer sequencing data were downloaded from TCGA database,and the differential gene lncRNA XIST was selected.The expression level of lncRNA XIST in pancreatic cancer cell lines was detected by qRT-PCR.The lncRNA XIST overexpression cell line of PANC-1 cells was constructed by transfection of lncRNA XIST overexpression vector.Evaluate the changes in the proliferation,migration and invasion ability of PANC-1 cells after lncRNA XIST overexpressed.The protein expression levels ofβ-catenin,Vimentin and N-cadherin in PANC-1 cells with overexpressed lncRNA XIST were detected by qRT-PCR and Western blotting.Results The expression of lncRNA XIST was down-regulated in pancreatic cancer(P<0.05).Among the PANC-1,PC-2,SW1990 and CFPAC-1 cells,the expression of lncRNA XIST was the lowest in PANC-1 cells.The overexpressed lncRNA XIST reduced the proliferation,migration and invasion ability of PANC-1 cells(P<0.05).It also down-regulated the expression level ofβ-catenin,but had no significant effects on the expression levels of Vimentin and N-cadherin(P>0.05).Conclusion lncRNA XIST was down-regulated in pancreatic cancer cells.Overexpressed lncRNA XIST restrained the proliferation,migration and invasion of pancreatic cancer cells by activating the Wnt/β-catenin pathway.